Dermal pharmacokinetics of the insecticide furathiocarb in rats

Liu, Kwang-Hyeon; Sung, Ha‐Jung; Lee, Hae-Keun; Song, Biao; Ihm, Yang-Bin; Kim, Kyun; Lee, Hye-Suk; Kim, Jeong‐Han

doi:10.1002/ps.422

Cited by 15 publications

(9 citation statements)

References 17 publications

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“…Although these products are generally less toxic than the parent compound, more toxic metabolites may also occur, as in the cases of parathion (Chambers et al, 1991) and malathion (Buratti et al, 2005). Such in vitro studies with microsomal preparations provide specific details of the chemical identity of metabolites and intermediates, the pattern of their formation, and the metabolic pathways of xenobiotics (Liu et al, 2002;Liu and Kim, 2003;Kim et al, 2005a).…”

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confidence: 99%

Stereoselective Metabolism of Endosulfan by Human Liver Microsomes and Human Cytochrome P450 Isoforms

Lee

Moon²,

Chang³

et al. 2006

Drug Metab Dispos

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ABSTRACT:Endosulfan (6,7,8,9,10,10-hexachloro-1,5,5a,6,9,9a-hexahydro-6,9-methano-2,3,4-benzo(e)dioxathiepin-3-oxide) is a broad-spectrum chlorinated cyclodiene insecticide. This study was performed to elucidate the stereoselective metabolism of endosulfan in human liver microsomes and to characterize the cytochrome P450 (P450) enzymes that are involved in the metabolism of endosulfan. Human liver microsomal incubation of endosulfan in the presence of NADPH resulted in the formation of the toxic metabolite, endosulfan sulfate. The intrinsic clearances (CL int ) of endosulfan sulfate from ␤-endosulfan were 3.5-fold higher than those from ␣-endosulfan, suggesting that ␤-endosulfan would be cleared more rapidly than ␣-endosulfan. Correlation analysis between the known P450 enzyme activities and the rate of the formation of endosulfan sulfate in the 14 human liver microsomes showed that ␣-endosulfan metabolism is significantly correlated with CYP2B6-mediated bupropion hydroxylation and CYP3A-mediated midazolam hydroxylation, and that ␤-endosulfan metabolism is correlated with CYP3A activity. The P450 isoform-selective inhibition study in human liver microsomes and the incubation study of cDNA-expressed enzymes also demonstrated that the stereoselective endosulfan sulfate formation from ␣-endosulfan is mediated by CYP2B6, CYP3A4, and CYP3A5, and that from ␤-endosulfan is mediated by CYP3A4 and CYP3A5. The total CL int values of endosulfan sulfate formation catalyzed by CYP3A4 and CYP3A5 were consistently higher for ␤-endosulfan than for the ␣-form (CL int of 0.67 versus 10.46 l/min/pmol P450, respectively). CYP2B6 stereoselectively metabolizes ␣-endosulfan, but not ␤-endosulfan. These findings suggest that the CYP2B6 and CYP3A enzymes are major enzymes contributing to the stereoselective disposition of endosulfan.

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confidence: 99%

Stereoselective Metabolism of Endosulfan by Human Liver Microsomes and Human Cytochrome P450 Isoforms

Lee

Moon²,

Chang³

et al. 2006

Drug Metab Dispos

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“…This insecticide can be applied to kill insects that inhabit the soil (PPDB, 2009). Furatiocarb can be genotoxic by inducing mutations and may cause conversion of mitotic genes with increased mitotic chromosomal loss in Saccharomyces cerevisiae [67] strains and is also considered neurotoxin and endocrine disrupting PPDB, [68]. Through the biotransformation process they produce the metabolites carbofuran, 3-hydroxycarbofuran and 3-ketocarbofuran in biological tissues such as liver and kidney [69][70][71][72][73].…”

Section: Toxicological Analyzes On Rainbow Trout (Gills Liver and Mumentioning

confidence: 99%

Presence of Organic Pesticides in Commercial Rainbow Trout Farms

Filho¹

2018

BJSTR

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“…The cleavage of the N-S bond gave carbofuran (Marsden et al 1982). Furathiocarb was found to be metabolized to carbofuran and 3-hydroxycarbofuran following dermal treatment (Liu et al 2001(Liu et al , 2002. However, virtually no information is available on the dermal penetration through rat skin, which could be an important factor for the human exposure risk assessment.…”

Section: Introductionmentioning

confidence: 99%

In vitro dermal penetration study of carbofuran, carbosulfan, and furathiocarb

Liu

Kim

2003

Arch Toxicol

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In this study, the dermal penetration rate of carbofuran, carbosulfan, and furathiocarb has been measured with rat abdominal skin using the static diffusion cell. The technical grades of three compounds were applied at different doses on skin surface mounted in static diffusion cell and incubated at 32 degrees C for 48 h with shaking. The same procedures were carried out with furathiocarb EC (emulsifiable concentrate) and WP (wettable powder). At regular intervals, the receptor fluid in cell was sampled and analyzed by HPLC. Only carbofuran was found in carbosulfan- or furathiocarb-treated samples, suggesting they converted into carbofuran while passing through the skin layer. The quantity of insecticide penetrating skin increased with time and applied dose. The skin penetration rate increased with the water solubility of insecticides. The dermal penetration rates of carbofuran, furathiocarb, and carbosulfan were determined as 1.05 micro g/cm(2) per h ( r(2)=0.991), 0.46 micro g/cm(2) per h ( r(2)=0.984) and 0.14 micro g/cm(2) per h ( r(2)=0.967), respectively. There was no significant difference in rate of skin penetration between furathiocarb EC (1.42 micro g/cm(2) per h, r(2)=0.988) and WP (1.35 micro g/cm(2) per h, r(2)=0.982), while furathiocarb technical grade showed a lower skin penetration rate. In vitro models may be used to predict percutaneous absorption and are useful in selecting safer formulations for field application of pesticide.

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Dermal pharmacokinetics of the insecticide furathiocarb in rats

Cited by 15 publications

References 17 publications

Stereoselective Metabolism of Endosulfan by Human Liver Microsomes and Human Cytochrome P450 Isoforms

Stereoselective Metabolism of Endosulfan by Human Liver Microsomes and Human Cytochrome P450 Isoforms

Presence of Organic Pesticides in Commercial Rainbow Trout Farms

In vitro dermal penetration study of carbofuran, carbosulfan, and furathiocarb

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